20-10641432-CAA-CAAA

Position:

• chr20-10641432-CAA-CAAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000214.3(JAG1):​c.2916+27dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1537 hom., cov: 0)
  • Exomes 𝑓: 0.15 (5575 hom.)
• Consequence: JAG1 NM_000214.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.173

Genes affected

JAG1 (HGNC:6188): (jagged canonical Notch ligand 1) The jagged 1 protein encoded by JAG1 is the human homolog of the Drosophilia jagged protein. Human jagged 1 is the ligand for the receptor notch 1, the latter is involved in signaling processes. Mutations that alter the jagged 1 protein cause Alagille syndrome. Jagged 1 signalling through notch 1 has also been shown to play a role in hematopoiesis. [provided by RefSeq, Nov 2019]

JAG1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 20-10641432-C-CA is Benign according to our data. Variant chr20-10641432-C-CA is described in ClinVar as [Benign]. Clinvar id is 1260067.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAG1	NM_000214.3	c.2916+27dupT		intron_variant		ENST00000254958.10	NP_000205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAG1	ENST00000254958.10	c.2916+27dupT		intron_variant		1	NM_000214.3	ENSP00000254958.4
JAG1	ENST00000423891.6	n.2782+27dupT		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.139 AC: 20713 AN: 149082 Hom.: 1536 Cov.: 0

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.00197

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.123

GnomAD4 exome AF: 0.151 AC: 200270 AN: 1329438 Hom.: 5575 Cov.: 13 AF XY: 0.149 AC XY: 99144 AN XY: 663966

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.132

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.00179

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.135

GnomAD4 genome AF: 0.139 AC: 20725 AN: 149182 Hom.: 1537 Cov.: 0 AF XY: 0.134 AC XY: 9740 AN XY: 72758

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.00197

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.121

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3215563; hg19: chr20-10622080;